For regionally-advanced or metastatic carcinoma (Ca) of the breast, combination chemotherapy may achieve local control and improve survival. It is used in project A to shrink primary masses and treat overt or micrometastases. Twenty-seven patients (15 with metastases and 13/27 with inflammatory Ca) were treated with combination chemotherapy. All 13 with inflammatory Ca had elimination of the inflammatory component. Twenty-four of the 27 were operable after chemotherapy and 22 had mastectomies. Five patients achieved partial remission prior to surgery and responded after surgery to achieve complete remission. Trials in metastatic disease must stratify for prognostic variables, thus cooperative group efforts are necessary. Project B compared 3 regimens for response rate and survival duration and found CAF to be superior. MER immunotherapy was detrimental. The successor study evaluates the role of tamoxifen hormonal therapy with the CAF combination. As of April 1981, 90 patients were entered onto study and interim analysis shows no differences. New combinations are needed for patients with refractory tumors. Project C evaluates the new combinations: mitomycin-C + vinblastine and doxorubicin + VP16. With 30 and 26 patients entered, both are highly active combinations. Project D looks at new drugs in advanced refractory disease.